A Phase I Trial of the Alpha Particle-emitting Radiopharmaceutical, Af-001, in Patients With Differentiated Thyroid Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Ph1b: Assessment of tumor reduction effect on MRI or CT scan images
研究概览
简要总结
This trial consists of 2 parts, i.e., Part Ia and Ib. The Part Ia is to evaluate the safety and tolerability of a single intravenous dose of af-001 in patients with radically unresectable, recurrent, metastatic differentiated thyroid cancer (papillary carcinoma, follicular carcinoma) refractory to or intolerant of standard-of-care therapy, who have received total thyroidectomy, and to determine the MTD (Maximum tolerated dose).
Part Ib is to evaluate the efficacy and safety of af-001 mutiple doses to patients with radically unresectable, recurrent, metastatic differentiated thyroid cancer (papillary carcinoma, follicular carcinoma), who have received total thyroidectomy and are RAI naïve, randomized into two arms at the determined MTD or the MTD-1 dose level, and to determine the recommended Phase II dose (RP2D)
详细描述
The Part Ia is a dose escalation part. The Part Ib is a parallel-group comparative study part based on the MTD determined in Part Ia, in which 10 patients each will be randomly assigned to one of two treatment arms, at the MTD for af-001 or the MTD-1 dose level. Patients will be randomly assigned by the enrollment system (allocated at a ratio of 1:1). Random assignment will be performed using the stratified permuted block method. The stratification factor will be the site(s) of metastases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •<Ia part>
- •Patients with differentiated thyroid cancer (papillary carcinoma, follicular carcinoma) after total thyroidectomy.
- •Patients with radically unresectable, recurrent, metastatic disease who are judged by the principal investigator or sub-investigator (hereinafter, "principal/sub-investigators") to be refractory to or intolerant of standard-of-care therapy.
- •<Ib part>
- •Patients with radically unresectable, recurrent, metastatic disease who are RAI naive
- •Patients with measurable lesions. <Ia/Ib part>
- •Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 and stable general condition.
- •Patients expected to survive for at least 6 additional months based on clinical symptoms and physical examination findings.
排除标准
- •<Ia/Ib part>
- •Patients who need to preserve fertility.
- •Females who are pregnant or may be pregnant, breastfeeding patients, or patients or their partners who cannot agree to appropriate contraception.
- •Patients with active multiple cancers (synchronous multiple cancers and ectopic double cancers with a disease-free period of <=3 years).
- •Patients with uncontrolled active infections.
- •Patients who are positive for hepatitis B virus surface (HBs) antigen, hepatitis C virus (HCV) antibodies, or human immunodeficiency virus (HIV) antibodies.
研究组 & 干预措施
[211At]NaAt
Ph1a: single dose, Ph1b: mutiple dose
干预措施: [211At]NaAt (Drug)
结局指标
主要结局
Ph1b: Assessment of tumor reduction effect on MRI or CT scan images
时间窗: 24 weeks
Using the "Revised version of the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 (Japanese translation of JCOG version 1.0)" as a reference.
Ph1a: DLT (Dose-limiting toxicity ) based on Japanese translation of the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, Japan Clinical Oncology Group (JCOG) version
时间窗: 4 weeks
DLT evaluation criteria: 1. Grade ≥4\* hematologic toxicity that persists for at least 7 days 2. Febrile neutropenia regardless of duration 3. Grade ≥3\* thrombocytopenia associated with a bleeding tendency or that requires platelet transfusions 4. Anemia that requires red blood cell transfusions 5. Neutropenia associated with infection 6. Grade ≥3\* non-hematologic toxicity that persists for at least 7 days and does not improve with symptomatic treatment, with the following exceptions: * Toxicities that can be controlled to Grade ≤2\* with maximum supportive herapy * Those due to the progression of the primary tumor \[\*: Grades as defined in CTCAE v.5.0 (Japanese translation) JCOG version\]
次要结局
未报告次要终点